The goal of this work is to elucidate the molecular mechanism underlying the ATP-dependent regulation of the shape of the red cell membrane. The work has focussed on the characterization of the phosphorylation of spectrin and the regulation of cyclic AMP-independent protein kinase and protein phosphatase which mediate this reaction. Our data suggests that spectrin is fully phosphorylated in situ, and in isolated membranes, shape changes which occur in ATP-dependent or independent modes are neither correlated with the degree of spectrin phosphorylation. We have partially purified spectrin kinase and the study of its cellular localization is underway. Spectrin phosphatase exists in membrane bound and cytoplasm forms and the partition and regulation of each form of this activity is under study. The present studies indicate that the spectrin phosphorylation reaction is not a critical determinant to red blood cell shape.